The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health...The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.展开更多
Gosnell and colleagues executed a large-scale cohort investigation delineating ethnic disparities in outcomes among individuals with metabolic dysfunction–as-sociated steatotic liver disease/steatohepatitis(MASLD/MAS...Gosnell and colleagues executed a large-scale cohort investigation delineating ethnic disparities in outcomes among individuals with metabolic dysfunction–as-sociated steatotic liver disease/steatohepatitis(MASLD/MASH).Uncovering such heterogeneity is pivotal to optimising management and prognostication,notably for hepatocellular carcinoma,fibrotic progression,and all-cause mortality.The authors furnish granular trajectories for Hispanic vs non-Hispanic popula-tions across the United States and southeastern Texas,alongside a comprehensive appraisal of MASLD/MASH-related event rates.These insights provide an indispensable framework for early risk stratification and the tailoring of thera-peutic algorithms and surveillance regimens.The study underscores the necessity for nuanced appreciation of MASLD/MASH outcome profiles and associated management strategies,while interrogating regional variation in disease burden,the benefits of integrated metabolic care,and the potential of lifestyle inter-ventions to attenuate complications and improve prognosis.展开更多
BACKGROUND Yes-associated protein 1(YAP1),a downstream transcriptional coactivator regulated by the Hippo signaling pathway,has been shown to be involved in liver fibrosis.YAP activity is modulated by G-protein couple...BACKGROUND Yes-associated protein 1(YAP1),a downstream transcriptional coactivator regulated by the Hippo signaling pathway,has been shown to be involved in liver fibrosis.YAP activity is modulated by G-protein coupled receptors,including Gαs-coupled protein dopamine receptor D1(DRD1).Levodopa,a dopamine precursor,activates DRD1 on cell surface,triggering its downstream signaling pathway.AIM To investigate the therapeutic effect of levodopa and the downstream mechanism on carbon tetrachloride(CCl_(4))-induced liver fibrosis,including liver DRD1 expression.METHODS SD rats were intraperitoneally injected with 40%CCl_(4)for 8 weeks to induce liver fibrosis,followed by treatment with varying doses of levodopa for 2 weeks.Serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels were measured,and liver pathology was assessed using hematoxylin and eosin and Masson's staining.Alpha-smooth muscle actin(α-SMA)content,along with the expressions of DRD1,YAP,and phosphorylated protein,was analyzed by Western blot,immunohistochemistry,and reverse transcription-quantitative real-time polymerase chain reaction.RESULTS Compared with the controls,levodopa-treated rats showed a decrease in the proportion of collagen in the liver and a recovery from liver fibrosis(P=0.0007).Western blot and immunohistochemistry indicated that DRD1 was upregulated in the fibrotic liver of rats treated with levodopa,showing an increase in DRD1 Level(P<0.0001).In addition,the upregulation of DRD1 activated the Hippo signaling pathway,manifested as increased YAP phosphorylation(P<0.05).CONCLUSION This was the first study to demonstrate that levodopa attenuates CCl_(4)-induced liver fibrosis by inhibiting the Hippo/YAP signaling pathways.展开更多
This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal o...This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal of Gastroenterology.The study explores the therapeutic potential of Fanlian Huazhuo formula(FLHZF)in treating metabolic-associated steatotic liver disease(MASLD),demonstrating that FLHZF reduces lipid accumulation,oxidative stress,and liver injury in MASLD models by modulating key signaling pathways involved in lipid metabolism and autophagy.This editorial emphasizes the potential of FLHZF as a treatment for MASLD and calls for further research to verify its clinical efficacy.展开更多
Introduction: Foot amputation in a diabetic patient is a real public health problem due to its functional and psychological repercussions. The objective was to study the factors associated with amputation in patients ...Introduction: Foot amputation in a diabetic patient is a real public health problem due to its functional and psychological repercussions. The objective was to study the factors associated with amputation in patients monitored for a diabetic foot in the internal medicine hospitalization of the Abass Ndao University Hospital Center (CHU) in Dakar. Methods: This was a retrospective, descriptive and analytical study conducted from the records of hospitalized patients over a 24-month period. The analysis included a descriptive phase, followed by a bivariate phase completed by logistic modeling following a descending procedure. Results: Of 1499 hospitalized patients, 224 cases had diabetic foot (14.9%). Among the cases of diabetic foot, 198 patients met the inclusion criteria. Their mean age was 61.7 ± 11.3 years, the sex ratio (M/F) was 1.2. Other associated cardiovascular risk factors were high blood pressure (54.0% 107 cases), and smoking (10.9% 21 cases). A history of lower limb amputation was found in 21.2% (42 cases). It was type 2 diabetes in 184 cases (92.9%) and the mean blood sugar was 2.7 ± 1.3 g/l. Chronic complications included neuropathy in 112 cases (78.3%), arteriopathy in 172 cases (86.9%), and chronic kidney disease in 167 cases (84.4%). The mean consultation time was 47.6 days. The main lesions were gangrene (64.6%), ulcer (24.7%), phlegmon (5.6%), and necrotizing fasciitis (5.1%). According to the University of Texas classification, patients presented with a stage D lesion (86.4%), grade 3 (51.0%). The hospital prevalence of amputation was 57.6% (114 cases), including major amputation in 55.1% (109 cases). The mortality rate was 36.4% (72 cases). Risk factors for amputation were peripheral arterial disease (ORa = 4.96 [1.33 - 18.43] p = 0.017), foot gangrene (Ora = 3.16 [1.24 - 8.04] p = 0.016) and Texas classification grade 3 (ORa = 17.49 [1.67 - 190] p = 0.019). Conclusion: The prevalence of foot and amputations remains a health problem. Reducing amputations will necessarily require strengthening prevention through education and early monitoring of diabetic patients.展开更多
Introduction: Uterine rupture is certainly one of the most serious, as it immediately jeopardises the vital prognosis of the mother and foetus. It is a common obstetric tragedy in our delivery rooms in countries with ...Introduction: Uterine rupture is certainly one of the most serious, as it immediately jeopardises the vital prognosis of the mother and foetus. It is a common obstetric tragedy in our delivery rooms in countries with limited resources, reflecting the poor quality of obstetric care and, consequently, an unmet obstetric need. Methods: This was a descriptive and analytical cross-sectional study with prospective data collection over a four-year period from 1 January 2020 to 31 December 2023 at the University Hospital Centre (CHU) of Bouaké, in the Obstetrics and Gynaecology Department. The variables studied were epidemiological characteristics, therapeutic aspects and factors associated with maternal. Results: The prevalence of uterine rupture was 0.63%. The average age was 32, with patients aged 35 and over accounting for 33.68%, married 44.21% and 70% not in education. Patients with uterine rupture had been evacuated in 85.26% of cases. Uterine rupture was diagnosed in 97.89% of cases during labour. Maternal lethality due to rupture was 15.79%. The causes of maternal death were dominated by haemorrhagic shock (53.33%). Factors statistically associated with death were age ≥ 35 years (OR: 3.14), duration of labour ≥ 12 hours (OR: 5.8), multiparity (OR: 19.04), admission delay beyond 2 hours (OR: 4.36), haemoglobin level ≤ 7 g/dl (OR: 36.84), coma or obnubilation (OR: 71.82), haemorrhagic shock (OR: 243.94) and occurrence of post-operative complications (OR: 76.45). Conclusion: The frequency of uterine rupture remains significant in the department (0.63%), with maternal mortality still high (15.79%). The key to reducing uterine rupture and its consequences lies in timely referral and early, appropriate management.展开更多
Digital sculpture is the product of the cross-integration of art and technology,and its development is accompanied by the two-way interaction between technological innovation and artistic concepts.Based on this,this p...Digital sculpture is the product of the cross-integration of art and technology,and its development is accompanied by the two-way interaction between technological innovation and artistic concepts.Based on this,this paper mainly analyzes the remolding of artistic creation logic by technical tools and the expansion of technical application boundary by artistic expression,and further reveals the dynamic balance relationship between the two in symbiosis,hoping to help understand the accompanying mechanism of art and technology in the digital age.展开更多
Hydrogen doping in associated gas combustion presents a promising strategy for mitigating carbon emissions from typically flared or vented gases.To support this idea,this study employed Chemkin Pro to model the lamina...Hydrogen doping in associated gas combustion presents a promising strategy for mitigating carbon emissions from typically flared or vented gases.To support this idea,this study employed Chemkin Pro to model the laminar premixed combustion of associated gases and conducted a sensitivity analysis of key combustion factors.The results demonstrated that increasing the hydrogen-doping ratio accelerated flame propagation and reduced combustion product accumulation time,while also elevating flame instability and inducing cracks or folds on the flame front at higher ratios.Notably,flame speed exhibited a 40%increase per 10%rise in the hydrogen-doping ratio,which directly enhanced combustion efficiency.Flame temperature peaked at an equivalence ratio of 1,whereas flame speed enhancement was maximized at a ratio of 1.3.Higher premix temperatures increased flame speed,and elevated combustion pressures raised flame temperature(stabilizing above 1 atm),with flame speed peaking at 0.06 atm.Critically,hydrogen doping below 15%minimally altered flame morphology,but 30%doping caused significant flame retraction toward the nozzle,which increased the flashback risk and raised NOx emissions by nearly one third.These findings provide insights for optimizing hydrogen-doped combustion processes to balance efficiency gains while ensuring operational safety and emission control.展开更多
BACKGROUND Kidney is the vital organ that plays a great role in maintaining an optimal internal environment.The normal kidney function can be altered by physical injury or disease.Currently,chronic kidney disease(CKD)...BACKGROUND Kidney is the vital organ that plays a great role in maintaining an optimal internal environment.The normal kidney function can be altered by physical injury or disease.Currently,chronic kidney disease(CKD)is an increasing major health problem worldwide.In 2017,it was ranked as the 12th leading cause of death and is expected to rise to the 5th ranked cause of death by 2040.Therefore,early detection,increasing patients'awareness and treatment of CKD are required to hold the problem.However,despite its higher prevalence of hospitalized morbidity and mortality,little is known about the magnitude and associated factor of CKD in the Ethiopian context.Hence this study aimed to determine the magnitude of CKD and associated factors at Wolkite University Specialized Hospital(WKUSTH),South West Ethiopia.AIM To determine the magnitude,and associated factors of CKD in WKUSTH,Ethiopia.METHODS Institutional based cross-sectional study with secondary data was conducted from November 15,2021 to February 28,2022 at WKUSTH.Three hundred forty five(345)participants were selected by a convenient sampling technique.Creatinine and urea were measured using cobas311 fully automated chemistry analyzer and estimated glomerular filtration rate(eGFR)was calculated using CKD epidemiology collaboration formula.Sociodemographic and clinical data were collected by using a pretested questionnaire.Data were coded and entered into EpiData 3.1 version and exported to STATA version 14 for analysis.Bivariate analysis was used to screen candidate variables for multivariate analysis.In the multivariate analysis a P value<0.05 were considered statistically significant.RESULTS The magnitude of CKD by impaired eGFR were 54(15.7%)(95%CI:0.116-0.194).In multivariable analysis,older age[adjusted odds ratio(AOR)=5.91,95%CI:2.41-14.47)],hypertension(AOR=10.41,95%CI:4.55-23.81),diabetes mellitus(AOR=5.90,95%CI:2.14-16.23),high body mass index(AOR=3.0,95%CI:1.30-7.27),and anemia(AOR=2.94,95%CI:1.26-6.88)were independently associated with CKD.CONCLUSION The magnitude of CKD among adult patients admitted to WKUSTH was high.Hence,researchers need to do a population-based study and longitudinal study on the magnitude of CKD,associated factors.Estimation of GFR for all hospitalized patients might help to early detection of CKD and prevent complications.展开更多
Background and Objectives: Post-operative complications (POC) are new pathological phenomena occurring in the post-operative period and worsening the previous situation through their morbidity and mortality. Our aim w...Background and Objectives: Post-operative complications (POC) are new pathological phenomena occurring in the post-operative period and worsening the previous situation through their morbidity and mortality. Our aim was to determine the prevalence and preoperative factors associated with early POC at University Clinics of Kisangani (CUKIS). Methods: This was a cross-sectional study conducted in the CUKIS, Department of Surgery from 1 January 2014 to 31 December 2023. The target population consisted of all patients who had undergone full post-operative follow-up. A logistic regression model using RStudio version 4.4.0 software was used to determine the factors predicting early postoperative complications. Results: The prevalence of early POC was estimated at 35%, with surgical site infection the most frequent POC at 45.3%. After multivariate analysis using logistic regression, the social category of widow(er)s, transfer, previous laparotomy, acute generalised peritonitis, preoperative length of stay of more than 10 days and ASA score 2 and 5 were significant risk factors associated with the occurrence of POC in the preoperative period. Conclusion: Certain factors can predict the occurrence of POC. Knowledge of these factors can help practitioners to take useful measures before each surgical operation on a patient with these factors, with a view to preventing or managing POC.展开更多
BACKGROUND The interplay between immune cells and metabolic associated fatty liver disease(MAFLD)is a critical research frontier,bridging immunology and hepatology.The bibliometric findings can guide future research a...BACKGROUND The interplay between immune cells and metabolic associated fatty liver disease(MAFLD)is a critical research frontier,bridging immunology and hepatology.The bibliometric findings can guide future research and funding priorities in the field by highlighting key areas of focus and potential therapeutic targets.AIM To analyze the literature on immune cells and MAFLD,identifying research trends and future hotspots.METHODS A systematic search in the Web of Science Core Collection from January 1,2004 to May 20,2024,yielded 1936 articles on immune cells and MAFLD.Excluding nonresearch documents,the data were analyzed using R packages Cluster profiler,enrichplot,ggplot2,VOSviewer and CiteSpace.Visualizations were created for countries,institutions,authors,journals,fields,co-cited references,keywords,genes,and diseases,with gene a disease data from Citexs.RESULTS The field gained momentum in 2006,with the United States of America and China as leading contributors.Key research themes included oxidative stress,metabolic syndrome,liver fibrosis,and the role of Kupffer cells.Bioinformatics identified interleukin-6,tumor necrosis factor and signal transducer and activator of transcription 3 as central proteins in immune responses and inflammation,suggesting potential therapeutic targets for MAFLD.Clinically,these hub genes play pivotal roles in the pathogenesis of MAFLD.For instance,targeting the tumor necrosis factor signaling pathway could reduce inflammation,while modulating interleukin-6 and signal transducer and activator of transcription 3 expression may improve metabolic function,offering new strategies for MAFLD therapy.CONCLUSION This bibliometric analysis reports on the research hotspots and emerging trends in the field of immune cells and MAFLD,highlighting key proteins and potential therapeutic strategies through bioinformatics.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)has become a leading cause of chronic liver disease,closely linked with metabolic syndrome.Recent evidence spotlights the gut–liver axis as a major playe...Metabolic dysfunction-associated steatotic liver disease(MASLD)has become a leading cause of chronic liver disease,closely linked with metabolic syndrome.Recent evidence spotlights the gut–liver axis as a major player in MASLD pathogenesis.Dysbiosis of gut microbiota alters the intestinal barrier and enhances endotoxemia,hepatic inflammation,insulin resistance and fibrosis.Microbial metabolites including short-chain fatty acids,bile acids and ethanol impact host metabolism and immunity,and their dysregulation contributes to disease progression.This review summarises the mechanistic associations between dysbiosis and MASLD involving altered microbial composition,leaky gut,toll-like receptor signalling and immune dysregulation.It also reviews microbially targeted therapeutic strategies,such as probiotics,prebiotics,synbiotics,faecal microbiota transplantation,diet changes,and postbiotic metabolites.Although these interventions may have clinical potential,the heterogeneity of outcomes highlights the interindividual nature of the microbiome and warrant personalized interventions.Developments in multi-omics and precision medicine provide possibilities to discover microbial biomarkers and customize therapeutic approach.Resolving methodological heterogeneity and providing a clear definition of MASLD-related dysbiosis are key for translating microbiome science into the clinic.In conclusion,modulation of gut microbiota is an emerging strategy for the adjunctive treatment of MASLD alongside lifestyle and pharmacologic therapies.展开更多
Background:Strengthening the patient safety culture is essential for improving healthcare service quality and ensuring patient safety.The study's aim was to investigate the current status of patient safety culture...Background:Strengthening the patient safety culture is essential for improving healthcare service quality and ensuring patient safety.The study's aim was to investigate the current status of patient safety culture in traditional Chinese medicine institutions and its associated factors to provide scientific recommendations for improvement.Methods:This cross‐sectional study was conducted October 14–18,2024.Four traditional Chinese medicine institutions in Zhejiang Province,China,were selected using convenience sampling,and the expected sample size was 544 participants.Data were collected using the Hospital Survey on Patient Safety Culture questionnaire,which comprises two sections:individual characteristics and patient safety culture.The latter comprises 10 dimensions with 32 items rated on a five‐point Likert scale.Dimension scores were calculated as the mean of corresponding item scores,and the overall score as the mean of all dimension scores.Descriptive statistics,t‐tests,analysis of variance,and multiple linear regression were used to analyze current status and associated factors of patient safety culture.Results:A total of 522 valid questionnaires were collected.The average patient safety culture score was 3.92.Among the dimensions,“F Communication About Error”received the highest score and“H Reporting Patient Safety Events”the lowest score.Age,monthly income,hospital grade,professional title,and weekly working hours were identified as independent factors associated with patient safety culture.Conclusion:The overall patient safety culture in the traditional Chinese medicine institutions of Zhejiang Province is relatively high but is affected by multiple factors.Further efforts are needed to implement diverse strategies aimed at strengthening patient safety culture within traditional Chinese medicine institutions.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)significantly contributes to cardiovascular morbidity,with cardiovascular disease being the leading cause of mortality among affected individuals.Atrial f...Metabolic dysfunction-associated steatotic liver disease(MASLD)significantly contributes to cardiovascular morbidity,with cardiovascular disease being the leading cause of mortality among affected individuals.Atrial fibrillation(AF),the most common cardiac arrhythmia,is frequently observed in patients with MASLD.While shared metabolic risk factors such as obesity,diabetes,dyslipidemia,and hypertension are implicated,underlying pathophysiological mechanisms that include systemic inflammation,oxidative stress,insulin resistance,endothelial dysfunction,and activation of the renin-angiotensin-aldosterone system(RAAS)are proposed to play significant part in the increased risk of AF in MASLD.The aim is to review the pathogenesis linking MASLD and AF.A comprehensive literature review was conducted,focusing on studies that explore the epidemiology,pathogenesis,and clinical implications of MASLD and AF.Databases searched included PubMed,Scopus,and Web of Science,with keywords such as"metabolic associated steatotic liver disease","non fibrotic metabolic associated steatohepatitis","Nonalcoholic fatty liver disease","metabolic syndrome","atrial fibrillation","antifibrotic therapies","pathogenesis",and"cardiovascular risk".Chronic low-grade inflammation and oxidative stress in MASLD contribute to atrial structural and electrical remodeling,fostering an arrhythmogenic substrate.Insulin resistance,a hallmark of MASLD,exacerbates metabolic dysfunction and promotes atrial fibrosis.Dysregulated lipid metabolism and gut microbiota alterations further compound cardiovascular risk.Aldosterone dysregulation and systemic inflammation stemming from RAAS activation contributes to the shared pathophysiology.The severity of MASLD does not seem to directly influence the risk of AF,suggesting that even early stages of liver disease can increase susceptibility to this arrhythmia.Effective management of MASLD requires targeted risk-factor modification strategies,including weight management,glycemic control,and pharmacological interventions.A multidisciplinary approach is essential for comprehensive assessment and management of MASLD patients,with a focus on cardiovascular risk assessment and arrhythmia prevention.Future research should explore the impact of emerging MASLD therapeutic agents on the incidence and recurrence of cardiac arrhythmias.Early detection and comprehensive management of MASLD and AF are crucial to mitigate the dual burden of these conditions.展开更多
Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional seve...Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional severe manifestations like meningoencephalitis and myocarditis.展开更多
Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown rem...Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown remarkable potential in cancer theranostics.展开更多
The process mineralogy of kaolin associated quartz flotation concentrate was studied.The experimental results show that the content of SiO2 in the flotation concentrate is 99.66%,and the main impurity elements in the ...The process mineralogy of kaolin associated quartz flotation concentrate was studied.The experimental results show that the content of SiO2 in the flotation concentrate is 99.66%,and the main impurity elements in the concentrate are Al,Fe,K,and Na.The gangue minerals in the flotation concentrate are mainly mica and feldspar symbiosis with quartz in the form of connexion or mineral inclusion.By taking the flotation concentrate as the raw material,the experimental research on HF concentration,HCl concentration,HNO3 concentration,acid leaching temperature,acid leaching time,and the leaching liquid solid ratio of hot pressing acid leaching conditions was carried out.Finally,the factors affecting the quality of purified products were analyzed.Through the acid leaching experiment,it can be seen that hydrofluoric acid has a greater effect on Al and Fe elements,hydrochloric acid has a greater effect on Fe elements,and nitric acid concentration has a smaller effect on impurity elements(which can also be confirmed from the thermodynamic analysis);the acid leaching temperature,the acid leaching time,and the leaching liquid solid mass ratio are proportional to the acid leaching effect.The Al content decreases from 1304.73 to 214.10μg/g,and the aluminum removal rate is 86.12%.The Fe content decreases from 39.35 to 3.72μg/g,and the iron removal rate is 90.55%.Thermodynamic and kinetic studies show that at 220℃,the chemical reaction between quartz and gangue minerals and the leaching agent can be spontaneous in the direction of positive reaction,and gangue minerals and the leaching agent had priority reaction.The mixed acid leaching process accords with the diffusion control model,Ea is 15.16 kJ/mol,which can provide a theoretical guidance for the purification of quartz.展开更多
Because human immunodeficiency virus(HIV)-associated Burkitt lymphoma(BL)has a poor prognosis new therapeutic approaches need to be developed1.Axicabtagene ciloleucel(axi-cel)is an anti-CD19 CAR-T cell commercially av...Because human immunodeficiency virus(HIV)-associated Burkitt lymphoma(BL)has a poor prognosis new therapeutic approaches need to be developed1.Axicabtagene ciloleucel(axi-cel)is an anti-CD19 CAR-T cell commercially available FDA-approved product for patients with relapsed or refractory(R/R)large B-cell lymphoma(LBCL).However,axi-cel has not been approved by the FDA for use in patients with R/R BL.展开更多
The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell d...The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.展开更多
Pulmonary hypertension associated with congenital heart disease represents a significant challenge for clinicians due to its complex pathophysiology and diverse presentation.This patient population exhibits a broad sp...Pulmonary hypertension associated with congenital heart disease represents a significant challenge for clinicians due to its complex pathophysiology and diverse presentation.This patient population exhibits a broad spectrum of anatomical and hemodynamic abnormalities,with congenital heart disease-associated pulmonary arterial hypertension(PAH-CHD)comprising a significant proportion of pediatric pulmonary hypertension(PH)cases.Although progress in diagnostic methods and treatment options has been made,PH continues to be a major contributor to illness and death among affected pediatric patients,especially when diagnosis or treatment is postponed.This review aims to equip non-specialist clinicians with a better understanding of PH associated with congenital heart disease,focusing on its pathophysiology,clinical presentation,and diagnostic criteria.Key recommendations for evaluating and managing this fragile population are presented,emphasizing the importance of early recognition and multidisciplinary collaboration.As an increasing number of congenital heart disease patients reach adulthood,understanding its lifelong impacts becomes crucial for improving outcomes and creating tailored treatment approaches.展开更多
基金American Heart Association Award,No.24IVPHA1288417and FCT Fellowships,No.2022.13253.BDANA.
文摘The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.
文摘Gosnell and colleagues executed a large-scale cohort investigation delineating ethnic disparities in outcomes among individuals with metabolic dysfunction–as-sociated steatotic liver disease/steatohepatitis(MASLD/MASH).Uncovering such heterogeneity is pivotal to optimising management and prognostication,notably for hepatocellular carcinoma,fibrotic progression,and all-cause mortality.The authors furnish granular trajectories for Hispanic vs non-Hispanic popula-tions across the United States and southeastern Texas,alongside a comprehensive appraisal of MASLD/MASH-related event rates.These insights provide an indispensable framework for early risk stratification and the tailoring of thera-peutic algorithms and surveillance regimens.The study underscores the necessity for nuanced appreciation of MASLD/MASH outcome profiles and associated management strategies,while interrogating regional variation in disease burden,the benefits of integrated metabolic care,and the potential of lifestyle inter-ventions to attenuate complications and improve prognosis.
文摘BACKGROUND Yes-associated protein 1(YAP1),a downstream transcriptional coactivator regulated by the Hippo signaling pathway,has been shown to be involved in liver fibrosis.YAP activity is modulated by G-protein coupled receptors,including Gαs-coupled protein dopamine receptor D1(DRD1).Levodopa,a dopamine precursor,activates DRD1 on cell surface,triggering its downstream signaling pathway.AIM To investigate the therapeutic effect of levodopa and the downstream mechanism on carbon tetrachloride(CCl_(4))-induced liver fibrosis,including liver DRD1 expression.METHODS SD rats were intraperitoneally injected with 40%CCl_(4)for 8 weeks to induce liver fibrosis,followed by treatment with varying doses of levodopa for 2 weeks.Serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels were measured,and liver pathology was assessed using hematoxylin and eosin and Masson's staining.Alpha-smooth muscle actin(α-SMA)content,along with the expressions of DRD1,YAP,and phosphorylated protein,was analyzed by Western blot,immunohistochemistry,and reverse transcription-quantitative real-time polymerase chain reaction.RESULTS Compared with the controls,levodopa-treated rats showed a decrease in the proportion of collagen in the liver and a recovery from liver fibrosis(P=0.0007).Western blot and immunohistochemistry indicated that DRD1 was upregulated in the fibrotic liver of rats treated with levodopa,showing an increase in DRD1 Level(P<0.0001).In addition,the upregulation of DRD1 activated the Hippo signaling pathway,manifested as increased YAP phosphorylation(P<0.05).CONCLUSION This was the first study to demonstrate that levodopa attenuates CCl_(4)-induced liver fibrosis by inhibiting the Hippo/YAP signaling pathways.
文摘This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal of Gastroenterology.The study explores the therapeutic potential of Fanlian Huazhuo formula(FLHZF)in treating metabolic-associated steatotic liver disease(MASLD),demonstrating that FLHZF reduces lipid accumulation,oxidative stress,and liver injury in MASLD models by modulating key signaling pathways involved in lipid metabolism and autophagy.This editorial emphasizes the potential of FLHZF as a treatment for MASLD and calls for further research to verify its clinical efficacy.
文摘Introduction: Foot amputation in a diabetic patient is a real public health problem due to its functional and psychological repercussions. The objective was to study the factors associated with amputation in patients monitored for a diabetic foot in the internal medicine hospitalization of the Abass Ndao University Hospital Center (CHU) in Dakar. Methods: This was a retrospective, descriptive and analytical study conducted from the records of hospitalized patients over a 24-month period. The analysis included a descriptive phase, followed by a bivariate phase completed by logistic modeling following a descending procedure. Results: Of 1499 hospitalized patients, 224 cases had diabetic foot (14.9%). Among the cases of diabetic foot, 198 patients met the inclusion criteria. Their mean age was 61.7 ± 11.3 years, the sex ratio (M/F) was 1.2. Other associated cardiovascular risk factors were high blood pressure (54.0% 107 cases), and smoking (10.9% 21 cases). A history of lower limb amputation was found in 21.2% (42 cases). It was type 2 diabetes in 184 cases (92.9%) and the mean blood sugar was 2.7 ± 1.3 g/l. Chronic complications included neuropathy in 112 cases (78.3%), arteriopathy in 172 cases (86.9%), and chronic kidney disease in 167 cases (84.4%). The mean consultation time was 47.6 days. The main lesions were gangrene (64.6%), ulcer (24.7%), phlegmon (5.6%), and necrotizing fasciitis (5.1%). According to the University of Texas classification, patients presented with a stage D lesion (86.4%), grade 3 (51.0%). The hospital prevalence of amputation was 57.6% (114 cases), including major amputation in 55.1% (109 cases). The mortality rate was 36.4% (72 cases). Risk factors for amputation were peripheral arterial disease (ORa = 4.96 [1.33 - 18.43] p = 0.017), foot gangrene (Ora = 3.16 [1.24 - 8.04] p = 0.016) and Texas classification grade 3 (ORa = 17.49 [1.67 - 190] p = 0.019). Conclusion: The prevalence of foot and amputations remains a health problem. Reducing amputations will necessarily require strengthening prevention through education and early monitoring of diabetic patients.
文摘Introduction: Uterine rupture is certainly one of the most serious, as it immediately jeopardises the vital prognosis of the mother and foetus. It is a common obstetric tragedy in our delivery rooms in countries with limited resources, reflecting the poor quality of obstetric care and, consequently, an unmet obstetric need. Methods: This was a descriptive and analytical cross-sectional study with prospective data collection over a four-year period from 1 January 2020 to 31 December 2023 at the University Hospital Centre (CHU) of Bouaké, in the Obstetrics and Gynaecology Department. The variables studied were epidemiological characteristics, therapeutic aspects and factors associated with maternal. Results: The prevalence of uterine rupture was 0.63%. The average age was 32, with patients aged 35 and over accounting for 33.68%, married 44.21% and 70% not in education. Patients with uterine rupture had been evacuated in 85.26% of cases. Uterine rupture was diagnosed in 97.89% of cases during labour. Maternal lethality due to rupture was 15.79%. The causes of maternal death were dominated by haemorrhagic shock (53.33%). Factors statistically associated with death were age ≥ 35 years (OR: 3.14), duration of labour ≥ 12 hours (OR: 5.8), multiparity (OR: 19.04), admission delay beyond 2 hours (OR: 4.36), haemoglobin level ≤ 7 g/dl (OR: 36.84), coma or obnubilation (OR: 71.82), haemorrhagic shock (OR: 243.94) and occurrence of post-operative complications (OR: 76.45). Conclusion: The frequency of uterine rupture remains significant in the department (0.63%), with maternal mortality still high (15.79%). The key to reducing uterine rupture and its consequences lies in timely referral and early, appropriate management.
文摘Digital sculpture is the product of the cross-integration of art and technology,and its development is accompanied by the two-way interaction between technological innovation and artistic concepts.Based on this,this paper mainly analyzes the remolding of artistic creation logic by technical tools and the expansion of technical application boundary by artistic expression,and further reveals the dynamic balance relationship between the two in symbiosis,hoping to help understand the accompanying mechanism of art and technology in the digital age.
基金supported by the China Postdoctoral Science Foundation(Grant No.2022M723497).
文摘Hydrogen doping in associated gas combustion presents a promising strategy for mitigating carbon emissions from typically flared or vented gases.To support this idea,this study employed Chemkin Pro to model the laminar premixed combustion of associated gases and conducted a sensitivity analysis of key combustion factors.The results demonstrated that increasing the hydrogen-doping ratio accelerated flame propagation and reduced combustion product accumulation time,while also elevating flame instability and inducing cracks or folds on the flame front at higher ratios.Notably,flame speed exhibited a 40%increase per 10%rise in the hydrogen-doping ratio,which directly enhanced combustion efficiency.Flame temperature peaked at an equivalence ratio of 1,whereas flame speed enhancement was maximized at a ratio of 1.3.Higher premix temperatures increased flame speed,and elevated combustion pressures raised flame temperature(stabilizing above 1 atm),with flame speed peaking at 0.06 atm.Critically,hydrogen doping below 15%minimally altered flame morphology,but 30%doping caused significant flame retraction toward the nozzle,which increased the flashback risk and raised NOx emissions by nearly one third.These findings provide insights for optimizing hydrogen-doped combustion processes to balance efficiency gains while ensuring operational safety and emission control.
文摘BACKGROUND Kidney is the vital organ that plays a great role in maintaining an optimal internal environment.The normal kidney function can be altered by physical injury or disease.Currently,chronic kidney disease(CKD)is an increasing major health problem worldwide.In 2017,it was ranked as the 12th leading cause of death and is expected to rise to the 5th ranked cause of death by 2040.Therefore,early detection,increasing patients'awareness and treatment of CKD are required to hold the problem.However,despite its higher prevalence of hospitalized morbidity and mortality,little is known about the magnitude and associated factor of CKD in the Ethiopian context.Hence this study aimed to determine the magnitude of CKD and associated factors at Wolkite University Specialized Hospital(WKUSTH),South West Ethiopia.AIM To determine the magnitude,and associated factors of CKD in WKUSTH,Ethiopia.METHODS Institutional based cross-sectional study with secondary data was conducted from November 15,2021 to February 28,2022 at WKUSTH.Three hundred forty five(345)participants were selected by a convenient sampling technique.Creatinine and urea were measured using cobas311 fully automated chemistry analyzer and estimated glomerular filtration rate(eGFR)was calculated using CKD epidemiology collaboration formula.Sociodemographic and clinical data were collected by using a pretested questionnaire.Data were coded and entered into EpiData 3.1 version and exported to STATA version 14 for analysis.Bivariate analysis was used to screen candidate variables for multivariate analysis.In the multivariate analysis a P value<0.05 were considered statistically significant.RESULTS The magnitude of CKD by impaired eGFR were 54(15.7%)(95%CI:0.116-0.194).In multivariable analysis,older age[adjusted odds ratio(AOR)=5.91,95%CI:2.41-14.47)],hypertension(AOR=10.41,95%CI:4.55-23.81),diabetes mellitus(AOR=5.90,95%CI:2.14-16.23),high body mass index(AOR=3.0,95%CI:1.30-7.27),and anemia(AOR=2.94,95%CI:1.26-6.88)were independently associated with CKD.CONCLUSION The magnitude of CKD among adult patients admitted to WKUSTH was high.Hence,researchers need to do a population-based study and longitudinal study on the magnitude of CKD,associated factors.Estimation of GFR for all hospitalized patients might help to early detection of CKD and prevent complications.
文摘Background and Objectives: Post-operative complications (POC) are new pathological phenomena occurring in the post-operative period and worsening the previous situation through their morbidity and mortality. Our aim was to determine the prevalence and preoperative factors associated with early POC at University Clinics of Kisangani (CUKIS). Methods: This was a cross-sectional study conducted in the CUKIS, Department of Surgery from 1 January 2014 to 31 December 2023. The target population consisted of all patients who had undergone full post-operative follow-up. A logistic regression model using RStudio version 4.4.0 software was used to determine the factors predicting early postoperative complications. Results: The prevalence of early POC was estimated at 35%, with surgical site infection the most frequent POC at 45.3%. After multivariate analysis using logistic regression, the social category of widow(er)s, transfer, previous laparotomy, acute generalised peritonitis, preoperative length of stay of more than 10 days and ASA score 2 and 5 were significant risk factors associated with the occurrence of POC in the preoperative period. Conclusion: Certain factors can predict the occurrence of POC. Knowledge of these factors can help practitioners to take useful measures before each surgical operation on a patient with these factors, with a view to preventing or managing POC.
基金Supported by Horizontal Project of Dongzhimen Hospital,No.HX-DZM-202343.
文摘BACKGROUND The interplay between immune cells and metabolic associated fatty liver disease(MAFLD)is a critical research frontier,bridging immunology and hepatology.The bibliometric findings can guide future research and funding priorities in the field by highlighting key areas of focus and potential therapeutic targets.AIM To analyze the literature on immune cells and MAFLD,identifying research trends and future hotspots.METHODS A systematic search in the Web of Science Core Collection from January 1,2004 to May 20,2024,yielded 1936 articles on immune cells and MAFLD.Excluding nonresearch documents,the data were analyzed using R packages Cluster profiler,enrichplot,ggplot2,VOSviewer and CiteSpace.Visualizations were created for countries,institutions,authors,journals,fields,co-cited references,keywords,genes,and diseases,with gene a disease data from Citexs.RESULTS The field gained momentum in 2006,with the United States of America and China as leading contributors.Key research themes included oxidative stress,metabolic syndrome,liver fibrosis,and the role of Kupffer cells.Bioinformatics identified interleukin-6,tumor necrosis factor and signal transducer and activator of transcription 3 as central proteins in immune responses and inflammation,suggesting potential therapeutic targets for MAFLD.Clinically,these hub genes play pivotal roles in the pathogenesis of MAFLD.For instance,targeting the tumor necrosis factor signaling pathway could reduce inflammation,while modulating interleukin-6 and signal transducer and activator of transcription 3 expression may improve metabolic function,offering new strategies for MAFLD therapy.CONCLUSION This bibliometric analysis reports on the research hotspots and emerging trends in the field of immune cells and MAFLD,highlighting key proteins and potential therapeutic strategies through bioinformatics.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has become a leading cause of chronic liver disease,closely linked with metabolic syndrome.Recent evidence spotlights the gut–liver axis as a major player in MASLD pathogenesis.Dysbiosis of gut microbiota alters the intestinal barrier and enhances endotoxemia,hepatic inflammation,insulin resistance and fibrosis.Microbial metabolites including short-chain fatty acids,bile acids and ethanol impact host metabolism and immunity,and their dysregulation contributes to disease progression.This review summarises the mechanistic associations between dysbiosis and MASLD involving altered microbial composition,leaky gut,toll-like receptor signalling and immune dysregulation.It also reviews microbially targeted therapeutic strategies,such as probiotics,prebiotics,synbiotics,faecal microbiota transplantation,diet changes,and postbiotic metabolites.Although these interventions may have clinical potential,the heterogeneity of outcomes highlights the interindividual nature of the microbiome and warrant personalized interventions.Developments in multi-omics and precision medicine provide possibilities to discover microbial biomarkers and customize therapeutic approach.Resolving methodological heterogeneity and providing a clear definition of MASLD-related dysbiosis are key for translating microbiome science into the clinic.In conclusion,modulation of gut microbiota is an emerging strategy for the adjunctive treatment of MASLD alongside lifestyle and pharmacologic therapies.
基金supported by two funding sources:(1)The Youth Program of the Humanities and Social Sciences Research Fund,Ministry of Education of China(Grant 18YJC630064)(2)Peking Union Medical College Hospital Talent Cultivation Program(Category C)(Grant UBJ12930).
文摘Background:Strengthening the patient safety culture is essential for improving healthcare service quality and ensuring patient safety.The study's aim was to investigate the current status of patient safety culture in traditional Chinese medicine institutions and its associated factors to provide scientific recommendations for improvement.Methods:This cross‐sectional study was conducted October 14–18,2024.Four traditional Chinese medicine institutions in Zhejiang Province,China,were selected using convenience sampling,and the expected sample size was 544 participants.Data were collected using the Hospital Survey on Patient Safety Culture questionnaire,which comprises two sections:individual characteristics and patient safety culture.The latter comprises 10 dimensions with 32 items rated on a five‐point Likert scale.Dimension scores were calculated as the mean of corresponding item scores,and the overall score as the mean of all dimension scores.Descriptive statistics,t‐tests,analysis of variance,and multiple linear regression were used to analyze current status and associated factors of patient safety culture.Results:A total of 522 valid questionnaires were collected.The average patient safety culture score was 3.92.Among the dimensions,“F Communication About Error”received the highest score and“H Reporting Patient Safety Events”the lowest score.Age,monthly income,hospital grade,professional title,and weekly working hours were identified as independent factors associated with patient safety culture.Conclusion:The overall patient safety culture in the traditional Chinese medicine institutions of Zhejiang Province is relatively high but is affected by multiple factors.Further efforts are needed to implement diverse strategies aimed at strengthening patient safety culture within traditional Chinese medicine institutions.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)significantly contributes to cardiovascular morbidity,with cardiovascular disease being the leading cause of mortality among affected individuals.Atrial fibrillation(AF),the most common cardiac arrhythmia,is frequently observed in patients with MASLD.While shared metabolic risk factors such as obesity,diabetes,dyslipidemia,and hypertension are implicated,underlying pathophysiological mechanisms that include systemic inflammation,oxidative stress,insulin resistance,endothelial dysfunction,and activation of the renin-angiotensin-aldosterone system(RAAS)are proposed to play significant part in the increased risk of AF in MASLD.The aim is to review the pathogenesis linking MASLD and AF.A comprehensive literature review was conducted,focusing on studies that explore the epidemiology,pathogenesis,and clinical implications of MASLD and AF.Databases searched included PubMed,Scopus,and Web of Science,with keywords such as"metabolic associated steatotic liver disease","non fibrotic metabolic associated steatohepatitis","Nonalcoholic fatty liver disease","metabolic syndrome","atrial fibrillation","antifibrotic therapies","pathogenesis",and"cardiovascular risk".Chronic low-grade inflammation and oxidative stress in MASLD contribute to atrial structural and electrical remodeling,fostering an arrhythmogenic substrate.Insulin resistance,a hallmark of MASLD,exacerbates metabolic dysfunction and promotes atrial fibrosis.Dysregulated lipid metabolism and gut microbiota alterations further compound cardiovascular risk.Aldosterone dysregulation and systemic inflammation stemming from RAAS activation contributes to the shared pathophysiology.The severity of MASLD does not seem to directly influence the risk of AF,suggesting that even early stages of liver disease can increase susceptibility to this arrhythmia.Effective management of MASLD requires targeted risk-factor modification strategies,including weight management,glycemic control,and pharmacological interventions.A multidisciplinary approach is essential for comprehensive assessment and management of MASLD patients,with a focus on cardiovascular risk assessment and arrhythmia prevention.Future research should explore the impact of emerging MASLD therapeutic agents on the incidence and recurrence of cardiac arrhythmias.Early detection and comprehensive management of MASLD and AF are crucial to mitigate the dual burden of these conditions.
文摘Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional severe manifestations like meningoencephalitis and myocarditis.
基金supported by the grants provided by Zhuhai People's Hospital,China(Grant No.:2021KYQD-03)the National Natural Science Foundation of China(Grant No.:22176016).
文摘Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown remarkable potential in cancer theranostics.
文摘The process mineralogy of kaolin associated quartz flotation concentrate was studied.The experimental results show that the content of SiO2 in the flotation concentrate is 99.66%,and the main impurity elements in the concentrate are Al,Fe,K,and Na.The gangue minerals in the flotation concentrate are mainly mica and feldspar symbiosis with quartz in the form of connexion or mineral inclusion.By taking the flotation concentrate as the raw material,the experimental research on HF concentration,HCl concentration,HNO3 concentration,acid leaching temperature,acid leaching time,and the leaching liquid solid ratio of hot pressing acid leaching conditions was carried out.Finally,the factors affecting the quality of purified products were analyzed.Through the acid leaching experiment,it can be seen that hydrofluoric acid has a greater effect on Al and Fe elements,hydrochloric acid has a greater effect on Fe elements,and nitric acid concentration has a smaller effect on impurity elements(which can also be confirmed from the thermodynamic analysis);the acid leaching temperature,the acid leaching time,and the leaching liquid solid mass ratio are proportional to the acid leaching effect.The Al content decreases from 1304.73 to 214.10μg/g,and the aluminum removal rate is 86.12%.The Fe content decreases from 39.35 to 3.72μg/g,and the iron removal rate is 90.55%.Thermodynamic and kinetic studies show that at 220℃,the chemical reaction between quartz and gangue minerals and the leaching agent can be spontaneous in the direction of positive reaction,and gangue minerals and the leaching agent had priority reaction.The mixed acid leaching process accords with the diffusion control model,Ea is 15.16 kJ/mol,which can provide a theoretical guidance for the purification of quartz.
基金supported by the Sponsored by Tianjin Health Research Project(Grant No.TJWJ2023ZD003)the Chinese Society of Clinical Oncology Beijing Xisike Clinical Oncology Research Foundation(Grant Nos.Y-NCJH202201-0027 and Y-2022YMJN/MS-0001).
文摘Because human immunodeficiency virus(HIV)-associated Burkitt lymphoma(BL)has a poor prognosis new therapeutic approaches need to be developed1.Axicabtagene ciloleucel(axi-cel)is an anti-CD19 CAR-T cell commercially available FDA-approved product for patients with relapsed or refractory(R/R)large B-cell lymphoma(LBCL).However,axi-cel has not been approved by the FDA for use in patients with R/R BL.
基金supported by the National Institutes of Health(Grants P30 CA036727 and R01 CA258621)and funding from the University of Nebraska Medical Center Graduate Studies Assistantship.
文摘The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.
文摘Pulmonary hypertension associated with congenital heart disease represents a significant challenge for clinicians due to its complex pathophysiology and diverse presentation.This patient population exhibits a broad spectrum of anatomical and hemodynamic abnormalities,with congenital heart disease-associated pulmonary arterial hypertension(PAH-CHD)comprising a significant proportion of pediatric pulmonary hypertension(PH)cases.Although progress in diagnostic methods and treatment options has been made,PH continues to be a major contributor to illness and death among affected pediatric patients,especially when diagnosis or treatment is postponed.This review aims to equip non-specialist clinicians with a better understanding of PH associated with congenital heart disease,focusing on its pathophysiology,clinical presentation,and diagnostic criteria.Key recommendations for evaluating and managing this fragile population are presented,emphasizing the importance of early recognition and multidisciplinary collaboration.As an increasing number of congenital heart disease patients reach adulthood,understanding its lifelong impacts becomes crucial for improving outcomes and creating tailored treatment approaches.
